Unmet needs in PKU and the disease impact on the day-to-day lives in Brazil: Results from a survey with 228 patients and their caregivers

Abstract

Background Accumulation of phenylalanine (Phe) due to deficiency in the enzyme phenylalanine hydroxylase (PAH), responsible for the conversion of Phe into tyrosine leads to Phenylketonuria (PKU), a rare autosomal recessive inborn error of metabolism with a mean prevalence of approximately 1:10,000 to 1:15,000 newborns. Physical, neurocognitive and psychiatric symptoms include neurodevelopmental disorder as intellectual disability and autism spectrum disorder. The most common treatments such as low-Phe diet and supplements may decrease blood Phe concentrations, but neuropsychological, behavioral and social issues still occur in some patients. This study aimed to better understand (i) the Brazilian population's knowledge about newborn screening (NBS), the main diagnostic method for PKU, as well as (ii) the impacts of phenylketonuria in the daily lives of patients and parents. Methods Two surveys in Real World Data format gathering of Brazilian residents by online questionnaires with (i) 1000 parents of children up to 5 years old between March and April 2019; (ii) 228 PKU patients and caregivers in March 2019. The survey was conducted in partnership with Abril Publisher and two Brazilian patient associations: Metabolic Mothers and SAFE Brasil, for families with rare diseases and PKU patients, respectively. Results The first questionnaire shows that 93% of parents recognize the importance of NBS and 92% report that their children have undergone the test. Still, two out of ten participants did not know what the exam is or what it is for. From the second questionnaire nine out of ten patients had their PKU diagnosis by NBS. Although strict dietary controls for PKU were claimed by 44% of respondents from second questionnaire, 55% assume not following all nutritionist recommendations and 52% did not maintain routinely Phe control levels. In addition, 53% said they had high spending on medical appointments, therapies and purchase of special foods. Conclusions Despite the lack of understanding, the awareness of NBS importance is present in the studied population. The early diagnosis of most PKU patients in the study corroborates with neonatal screening central role of PKU early detection. The difficulty in adhering to dietary adjustments and the possibility that current and new therapeutic strategies other than diet could be determinant to achieve the recommended Phe levels.

Burden of phenylketonuria in Latin American patients: a systematic review and meta-analysis of observational studies

“…Six of the included studies were published only as an abstract [ 13 – 19 ], ten studies as a thesis [ 20 – 29 ], and the majority (n = 57) were published as full-text in peer-reviewed journals [ 14 , 28 , 30 – 74 ]. Seven further studies [ 27 , 29 , 75 – 79 ] were published initially as a thesis followed by a full-text publication [ 34 , 43 , 80 – 83 ].…”

“…Sixty-four of the 79 included studies reported at least one patient-important outcome at individual or population level, and they are displayed in Table 1 for study characteristics. Regarding study design, 18 were case series [ 22 , 23 , 33 , 34 , 40 – 42 , 45 , 54 , 55 , 58 , 60 , 70 , 84 – 87 ], 47 cross-sectional studies [ 6 , 7 , 13 – 15 , 17 – 21 , 24 , 26 , 29 , 30 , 35 – 39 , 43 , 46 , 47 , 53 , 56 , 59 , 61 , 62 , 67 , 68 , 71 , 73 , 75 – 77 , 79 – 81 , 88 – 91 ], 13 case reports [ 34 , 44 , 48 , 51 , 63 , 64 , 69 , 74 , 84 , 87 , 92 – 94 ], and two cohort studies [ 57 , 95 ].…”

“…3 A, C; 4 D, and 5 Executive function deficit Peabody Picture Vocabulary Test—Number of patients classified as Low Sleeping disorders Sleeping disorder Socioeconomic impact Poor school performance Malloy-Diniz et al 2004 [ 61 ] £ Brazil 21 274 ¢ 61.9 NR Average phe level below 120 μmol/l Individual Neurological, neurocognitive and neuropsychiatric impairments Bayley Scale of Infant Development Early Phe-restricted diet 27.5** NA Not included as quantitative data on outcome of interest not provided in paper Executive function deficit A not B task Piaget Mancini et al 2010 [ 62 ] £$ Brazil 33 7.67 52.38 NR NR Individual Patient adherence to clinical recommendations Serum PKU Early Phe-restricted diet Up to 21 days of life NA Included in Fig. 4 E Martins et al 2020 [ 30 ] Brazil 228 Newborn, 90%; between 1 and 5 years old, 8%; and over 10 years old (2%) 21.49 NR NR Individual and economic ...…”

Unmet Needs of Children with Inherited Metabolic Disorders in the COVID-19 Pandemic

“…6 Children with RIMDs from both high-income and low- and middle-income countries (LMICs) had unmet needs before the pandemic. 7 - 9 Studies in the past years from mostly high-income countries have shown that the coronavirus disease 2019 (COVID-19) pandemic has negatively influenced the needs of both adults and children with a variety of rare diseases like immune deficiencies, genetic disorders. 10 - 15 Information is urgently needed specifically on the unmet needs of children with RIMDs during the COVID-19 pandemic, particularly in LMICs where the majority of such children reside.…”

Adaptation and Validation of a Questionnaire to Evaluate Knowledge of the Low Phe Diet in PKU

“…Initially, children with PKU will be guided by parents and later in adolescence and adulthood by self-management. This reduces the risks of cognitive decline in babies and mental and neurological problems in adults [ 11 , 12 ]. However, a low Phe diet during childhood but abandoned later in life can increase the risk of other adverse outcomes, such as depression, anxiety and executive functioning deficits in adulthood [ 13 ].…”